Rational combinations of radiation and chemotherapy which enhance tumor response and minimize normal tissue damage have not been derived clinically because of the lack of experimental data. The timing of chemotherapy relative to radiation is extremely important in this interaction and it is being studies at intervals from minus 64 to plus 64 hours. The studies are being conducted in five normal tissue systems and in a range of mouse tumor systems of different histology, including colon carcinoma, squamous cell carcinoma, breast carcinoma, lung carcinoma, and sarcoma. In addition, human tumors carried immunosuppressed nude mice are being used. Dose effect factors derived for tumor and normal tissue will be compared and the effect on the therapeutic ratio determined. When alterations of response that are beyond simple additivity of cell kill are found, the nature and basic mechanism of action causing such response will be evaluated.